DESCRIPTION (Applicant's Description Verbatim): Stem cells are defined as cells with the ability both to self renew and to differentiate. This property of stem cells underpins growth and differentiation during development and sustains homeostasis and repair processes throughout adult life. The identification of novel proteins that drive pluriopotent stem cell growth or factors that direct their differentiation and lineage commitment, are of fundamental significance in the understanding of stem cell biology and its medical applications. Central to the identification and characterization of these proteins is the availability of a super sensitive method for studying the protein expression profile of these cells under a wide range of conditions in a sensitive, quantitative, and efficient fashion. Alas, the prior-art techniques of differential display of proteins arc not sensitive enough and their dynamic detection range is not adequate for studying low abundance proteins. BIOTRACES has developed a proprietary Multi Photon Detection (MPD) technology. Using MPD technology, we are developing an integrated proteomic system including the MPD Imager for differential display of protein that is at least one hundred times more sensitive than other techniques. The purpose of this Phase I proposal is to apply MPD-based proteomics tools to identify and characterize proteins that are differentially modified or expressed during hematopoietic stem cells lineage commitment and differentiation. PROPOSED COMMERCIAL APPLICATION: MPD has successfully been applied to RNA/DNA analysis, immunoassays and proteomics. The MPD-enhanced analysis of proteins, including better immunoassays for cytokines will enable better biomedical diagnostics and new therapeutic modalities. This is a large, multi- billion dollar/yr market. BioTraces may become a dominant player in part of this market with income estimated to be in the range of 100-200 million dollars annually. We are developing MPD enabled ultrasensitive protein-chips, including the P-chip for stem cells. These new techniques permit us to capture a considerable segment of diagnostic proteomics and diagnostic oncology market.